Transduction of enterocytes with gene products may be used to augment or replace defective enzymes that are involved in absorption, secretion, and digestion. The main hypothesis is that viral transduction of intestinal stem cells with wild-type gene product will lower bilirubin levels in Gunn Rats that are deficient for bilirubin UDP-glucuronosyltransferase. The central goal of this study is to demonstrate that transduced intestinal stem cells can generate a transgenic mucosa that produces a sustained expression of a metabolically active enzyme. The research design involves the isolation and transduction of small bowel stem cells from neonatal Gunn rats with transplantation into adult rats. The specific aims address the ability to transduce isolated intestinal stem cells, to transplant the transduced stem cells back into adult Gunn rats with a reduction in bilirubin levels, and to demonstrate a sustain expression of gene product. This study will provide a basis for intestinal gene therapy as well as study of stem cell/mesenchyme interaction.